Comprehensive Preoperative Staging System for Endoscopic Juvenile Nasal Angiofibromas PDF

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Editor: OPEN ACCESS James I. Ausman, MD, PhD For entire Editorial Board visit : University of California, Los http://www.surgicalneurologyint.com Angeles, CA, USA SNI: Skull Base Original Article Comprehensive preoperative staging system for endoscopic single and multicorridor approaches to juvenile nasal angiofibromas Trichy N. Janakiram, Shilpee B. Sharma, Ekkehard Kasper1, Onkar Deshmukh, Iype Cherian2 Department of Otolaryngology, Royal Pearl Hospital, Tiruchirapally, Tamil Nadu, India, 1Department of Neurosurgical Oncology, BIDMC Cancer Center, Boston, Massachusetts, USA, 2Department of Neurological Surgery, COMS, Nepal E‑mail: *Trichy N. Janakiram ‑ [email protected]; Shilpee B. Sharma ‑ [email protected]; Ekkehard Kasper ‑ [email protected]; Onkar Deshmukh ‑ [email protected]; Iype Cherian ‑ [email protected] *Corresponding author Received: 03 August 16   Accepted: 04 January 17   Published: 26 April 17 Abstract Background: Juvenile nasal angiofibromas (JNA) is a benign lesion with high vascularity and propensity of bone erosion leading to skull base invasion and intracranial extension. It is known to involve multiple compartments, which are often surgically difficult to access. With evolution in surgical expertise and technical innovations, endoscopic and endoscopic‑assisted management has become the preferred choice of surgical management. Over the last four decades, various staging systems have been proposed, which are largely based on the extent of nasal angiofibroma. However, no clear guidelines exist for the stage‑appropriate surgical management. In this study, we aim to formulate a novel staging system based on the analysis of high quality preoperative imaging and propose detailed surgical guidelines related to disease stages as observed in 242 primary cases of JNA. Methods: A retrospective analysis of the case records of 242 primary JNA cases was performed at our center. Patients were staged according to various existing staging systems as well as our own new staging system, and outcome variables Access this article online were compared with respect to intraoperative blood loss, multiple staged operations, Website: and tumor recurrences. Operative records were studied and precise endoscopic www.surgicalneurologyint.com surgical guidelines were formulated for each stage. DOI: 10.4103/sni.sni_295_16 Results: Comparing the intraoperative blood loss seen in stages of various Quick Response Code: classifications, it was found that intraoperative blood loss correlated best and statistically significantly with stages in the newly proposed Janakiram staging system when compared to the existing staging systems. Staged operations were performed in a total of 7/242 patients, and there was a significant association between the requirement of a staged operation and tumor extent (Fischer’s exact test, P < 0.001). Tumor recurrence was seen in 22 cases and the pterygoid wedge This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Janakiram TN, Sharma SB, Kasper E, Deshmukh O, Cherian I. Comprehensive preoperative staging system for endoscopic single and multicorridor approaches to juvenile nasal angiofibromas. Surg Neurol Int 2017;8:55. http://surgicalneurologyint.com/Comprehensive-preoperative-staging-system-for-endoscopic-single-and-multicorridor-approaches-to-juvenile-nasal-angiofibromas/ © 2017 Surgical Neurology International | Published by Wolters Kluwer - Medknow Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 was found to be the most frequent site of recurrence initially. As the extent of resection improved with better surgical technique over time, recurrences were only found in superior orbital fissure, around the internal carotid artery, and in the middle cranial fossa. Conclusion: This new Janakiram staging system is based on preoperative imaging data from one of the largest JNA case series reported thus far. Respective guidelines reliably stratify patients into treatment groups with definite surgical approaches and predicts outcome. Improved surgical approaches in the modern endoscopic era have redefined JNA management with improved outcome. This study shows the importance of precise presurgical imaging and the choice of the most suitable surgical approach in reducing morbidity and mortality in JNA surgery. Key Words: Endoscopic excision, JNA, staging system INTRODUCTION to especially understand the degree of tumor invasion into the skull base and beyond. With this classification‑based Juvenile nasal angiofibromas (JNA) is a benign neoplastic surgical approach, we explore the suitability of exclusive lesion encountered in the anterior skull base, and is single transnasal corridor surgery as well as endoscopic characterized by significant vascularity and a propensity multicorridor approaches for these tumors. Based on of bone erosion with intracranial extension. Most our experience, we demonstrate that, with endoscopic authorities agree that surgery is the preferred modality of multicorridor approaches, we can stretch the limits of treatment, at least for primary tumors. JNA frequently endoscopic JNA resection to a new level. Only a small involves multiple anatomical compartments which are number of tumors that are very extensive will remain difficult to access. With growing expertise in endoscopic beyond management via such endoscopic‑controlled techniques and advancements in imaging, the endoscopic multicorridor approaches, and should, in our opinion, be route has evolved as the preferred approach for surgical resected by endoscopic‑assisted open approaches. management of JNA even at advanced tumor stages. Furthermore, in this study, new insights were gained Optimal imaging is an indispensable tool in the regarding the possible site of JNA origin and the common assessment and is the key element in planning surgery pathways of tumor spread, which can be inferred from for JNA. Adequately classifying the stage and precise observations made during surgery. extent of such a distinct pathology is essential, and will determine the most suitable operative approach as well as We discuss the implications of this assessment for the the extent of resection that can be achieved. This in turn overall management strategies of JNA, and it will be has profound implications on the prognosis. shown that this classification clearly correlates to the prognosis of the patient. Any staging system must continuously be updated to reflect changes in our knowledge of tumor characteristics or our understanding of recurrence patterns and MATERIALS AND METHODS how these features relate to available treatment options.[19,9] This new staging system, therefore, stratifies The entire medical and radiographic records of patients tumor extension into distinct subgroups and correlates who underwent endoscopic resection of JNA at our the extent of disease to stage‑appropriate definitive center between January 2005 and January 2014 were treatment strategies. retrospectively analyzed. In the present study, we analyze preoperative records Two hundred and forty‑two primary cases of JNA were of 242 consecutive JNA patients treated at our center identified for inclusion in this cohort analysis; all the over a period of 9 years. Based on our experience, we included patients were young males between 10 and propose and evaluate a new classification system that is 25 years of age. Cases were categorized and assigned derived from preoperative imaging data. Each stage in to groups according to the proposed Janakiram staging this classification system assigns patients to a specific system (JSS). The JSS takes into account the sites of treatment group with a defined surgical approach skull base involvement and the pattern of JNA extension appropriate to address specific issues encountered in based on preoperative imaging (see below). The most the respective anatomical compartment. Preoperative suitable approach and operative technique is then chosen computed tomography (CT) data was analyzed in detail according to this assigned stage. Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 Imaging Table 1: The staging system employed at our center for Preoperative evaluation included contrast‑enhanced CT JNA scan (0.625 mm) of the skull base and paranasal sinuses Stage 1a Pterygoid wedge and/or paranasal sinus obtained in three‑dimensional projections in both bone Stage 1b With extension to nasopharynx and soft tissue windowing. In advanced tumor cases Stage 2a With extension in nasal cavity and/minimal with orbital, parapharyngeal, or intracranial extension, involvement of pterygopalatine fossa additional magnetic resonance (MR) imaging with Stage 2b Involvement of infratemporal fossa contrast was obtained. Stage 2c Involvement of infratemporal fossa with extension to Patients with lesions in close proximity to or with cheek/pterygoid fossa/inferior orbital fissure/laterally involvement of the internal carotid artery (ICA) underwent along the greater wing of sphenoid additional conventional transfemoral angiography for Stage 3a Involvement of quadrangular space/Meckel’s cave identification of the tumor supplying vessels. Cases Stage 3b Involvement of cavernous sinus/engulfing carotid artery that involved the ICA to a significant degree underwent Stage 4a Prestyloid parapharyngeal tumor extension above the balloon occlusion testing to assess cross circulation. lower border of the mandible Preoperative embolization was not deemed necessary and Stage 4b Intracranial intradural extension hence not performed in any of our cases. Intraoperative Stage 5 Massive parapharyngeal, maximal intracranial navigation was used for all cases infiltrating the greater extensions, and bilateral JNA wing of sphenoid, tumors encasing the ICA, infiltrating the cavernous sinus, or extending intracranially. To avoid ICA injuries, microvascular Doppler sonography was used to localize the vessel intraoperatively. Postoperative evaluation included a contrast‑enhanced CT within 36 hours of surgery to identify any residual tumor burden. In cases in which any significant residual tumor mass was displayed, patients were taken back to the operation room electively for a second surgery session. a b In all cases of ICA transposition, a second conventional angiography was performed postoperatively. Postoperative follow‑up data included CT scanning immediately after resection, as described above, and at 6 months postoperatively, along with nasal endoscopic examinations every 3 months for the first year after surgery and every 6 months for the following 3 years as well as a comprehensive clinical exam at each visit. c d Additional scan was obtained if the endoscopy revealed Figure 1: Preoperative imaging in Janakiram staging system. any suspision for recurrence. Recurrent disease was (a) Tumor seen involving pterygoid wedge and paranasal sinus on defined as new tumor seen on subsequent imaging a coronal section CT scan (Stage 1a). (b) On a coronal section CT studies during the follow‑up observation period after an scan, tumor seen extending to the nasopharynx (Stage 1b). (c) Axial section CT scan showing tumor extension to the nasal cavity and initially negative postoperative scan. pterygopalatine fossa (Stage 2a). (d) Tumor seen extending to the infratemporal fossa in an axial section (Stage 2b) Staging system The JSS is based on tumor extent as seen on preoperative contrast‑enhanced CT. It consists of 5 stages and approach on prognosis. The surgical approaches in this substages as they relate to endoscopic surgery, as well geared system are gradually expanded in a stepwise as one separate advanced stage for rare JNA extensions, manner from a rather simple middle meatal antrostomy to which are beyond the access of endoscopic approaches. a complex modified Denker at our center for maximum Our staging system advocates a tailored surgical strategy exposure and increased surgical maneuverability. When for each anatomical tumor configuration depending transnasal endoscopic surgery via a single trajectory upon the various compartments involved. The staging reaches its limits and gross tumor resection is not system employed at our center for JNA is presented feasible, endoscopic multicorridor approaches were in Table 1 and illustrated in Figures 1–4. Cases with employed for further and eventually complete excision of similar anatomical configuration and comparable extent the tumor. Based on this staging system, we suggest that of disease are assigned to a distinct JSS Figure 5, which even very advanced tumors – that display extension into is approached in a consistent manner by our surgical complex and difficult to reach anatomical areas – can be protocol; then, we analyzed the impact of this categorical approached via multiple corridors or may be dealt with Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 in more than one surgical session. Finally, the system Table 2: Proposed stagewise surgical approach includes a stage that comprises rare tumors with extreme Stage 1a – Tumor limited to pterygoid wedge with or without sphenoid extensions that are beyond the access of endoscopic sinus [Figure 5] multicorridor approaches. The most suitable access to The exposure requires anterior and posterior ethmoidectomy with wide such massive tumors is best via external approaches, and sphenoidotomy. The blood loss is controlled by cauterization of the therefore, these cases (two cases) are not included in posterior nasal branch of the sphenopalatine artery followed by tumor the statistical analysis of this endoscopic staging system. excision. The pterygoid wedge is drilled and the residual tumor can be The management or external approach for such tumor accessed and delivered. depends upon the surgeons’ choice and expertise. Stage 1b – Extension into pterygoid wedge and sphenoid sinus with or without involvement of the nasopharynx [Figure 5] Surgical planning The exposure is achieved by wide middle meatus antrostomy. The General transoral endotracheal anesthesia was administered. sphenopalatine artery, descending palatine artery, and vidian artery can Hypotensive anesthesia (htA) was maintained using a be cauterized or clipped to devascularize the tumor. The tumor is finally nitroglycerine infusion. Goal in hypotensive anesthesia is dissected off the nasopharynx and delivered. The pterygoid wedge is to achieve mean arterial pressures of 60–70 mmHg and drilled away and residual tumor is removed. systolic blood pressure values at about 80–90 mm Hg. Stage 2a – Tumor with minimal extension into the pterygopalatine fossa with or without involvement of the nasal cavity [Figure 5] Hemodynamics were closely monitored with invasive access Exposure is obtained by medial maxillectomy with removal of the medial throughout the case. The four‑handed binostril technique part of the posterior wall of maxillary sinus. A posterior septectomy/ was used in all cases except in stage 1 cases. septal window is added to facilitate access with a four‑handed In the following paragraph [Table 2], we describe the binostril technique. Ligation of internal maxillary artery is done for surgical approach for each stage. devascularization. This vessel has to be carefully dissected and identified lateral to the tumor margin. Statistical analyses Stage 2b – Extension to pterygopalatine fossa/infratemporal A number of variables (tumor extension based on fossa [Figure 5] presurgical imaging, surgical approaches chosen, direct Endoscopic medial maxillectomy is performed for tumor exposure. Tumor vascular control by ligation of the feeder vessels, dissection is carried out after ligation of the internal maxillary artery, intraoperative blood loss, occurrence of residual or which is dissected lateral to the tumor margin. recurrent disease, and need for staged surgery) was Stage 2c – Involvement of infratemporal fossa with or without further extension into pterygoid space/inferior orbital fissure/laterally along analyzed for tumor staging and subsequently correlated the greater wing of sphenoid/cheek area [Figure 5] to clinical outcome. Transient clamping of the external carotid artery on the same side is The database of our cohort was also used to classify recommended and carried out prior to starting the endoscopic procedure our patient series according to other already established to control the blood loss for stage 2C and beyond. staging systems.[1,5,22,24,28,29] The respective outcomes were In this setting, a modified endoscopic Denker’s approach is used to expose the angiofibroma at its most lateral extent before commencing then correlated with the distinct stages of the proposed the tumor dissection. Trigeminal branch V2 is identified and should be JSS and compared to those of the existing classification preserved as it also serves as a landmark for inferior orbital fissure. In systems. Blood loss was recorded during surgery and JNA cases with tumor extension into the inferior orbital fissure, the bony amounts were correlated to the respective surgical margins are drilled away with a 3 mm diamond drill burr to facilitate approaches using the Spearman rank correlation. The exposure and allow extirpation of this part of the tumor. number of cases that required a staged procedure as Any tumor anterior to the pterygoid wedge is debulked first to enable well as the observation of tumor recurrence during the drilling of the involved cancellous bone. postsurgical observation period was also correlated to the Stage 3a – Involvement of quadrangular space/Meckel’s cave respective “classification stage” using Fischer’s exact test. [Figure 5] Statistical significance was defined when the calculated In cases with extension in to the quadrangular space or Meckel’s cave, a modified Denker’s approach with clamping of the external carotid artery level was at or below 0.05 (Software SPSS version 21 IBM is again performed. The tumor is debulked first so that the pterygoid SPSS Statistics for Windows, Version 22.0. Armonk, NY: wedge can be accessed, as described above. The drilling of the greater IBM Corp.). sphenoid wing superiorly is important for better proximal exposure, which aids in removing tumor from crevices in the cancellous bone. RESULTS It rarely extends laterally or superiorly to the anatomical path of V2. Further posterolateral extension beyond the pterygoid wedge is limited Demographics by middle cranial fossa dura. As the tumor respects the dura, it can be meticulously dissected away from it with gentle traction. Between January 2005 and January 2014, a total of The vidian nerve is then identified and can be freed by drilling out bone 242 JNA patients were identified as requiring surgery from the 6 to 9 o clock position. The anterolateral wall of the sphenoid is and were subsequently operated in our department. removed next. The paraclival ICA is identified. The bone over the medial All patients were males. The mean age at surgery was wall of the paraclival ICA is drilled away. The lingular process is identified 17.3 years (range = 10–25 years). All patients were fully and removed, which allows mobilization of the ICA. The paraclival worked up and their tumor was categorized according to Contd... Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 Table 2: Contd... Table 2: Contd... ICA can now be gently transposed medially, which creates additional corridor is bounded laterally by the temporalis muscle, posteromedially space to resect any tumor extending into Meckel’s cave. by the superior orbital fissure, and superiorly by the dura of the anterior Stage 3b – Involvement of cavernous sinus and/or engulfment of the cranial fossa. Using this corridor, the tumor is exposed lateral to the carotid artery [Figure 5] superior orbital fissure, and microsurgical dissection is performed with In this stage, the tumor resection till the level of the pterygoid wedge regular cauterization of the blood vessels using bipolar cautery prior to is performed, as described in the earlier stages. It can be delivered via delivery of the tumor mass. the oropharynx, as described above. The tumor is carefully debulked Stage 5 – Massive parapharyngeal, maximal intracranial extensions, in close proximity to the ICA. The microvascular Doppler probe can be and bilateral JNA used to identify the exact position of the ICA. Feeder vessels arising These include rare extensions of JNA that are beyond the access of from the ICA supplying the tumor can be cauterized. The tumor around multicorridor endoscopic approach. They can be dealt with external the ICA is carefully debulked in a piecemeal manner. The position of endoscopic‑assisted approaches. the ICA needs to be confirmed as well as its distance to the workspace In two cases with poststyloid parapharyngeal extension or bilateral that has been developed before opening the cavernous sinus. Tumor can JNAs, the author prefers an external approach to access the tumor. now be gently dissected off the sinus wall while taking care not to injure The external approach implemented by the author is a bilateral facial cranial nerves. Intraoperative monitoring and direct nerve stimulation translocation approach proposed by Ivo Janecka. However, the author is used for identification and monitoring of the integrity of cranial does not advocate any specific external approach. The choice of external nerves. Electrodes are introduced in superior rectus (CN III), superior approach is at the discretion of the provider. oblique (CN IV), temporalis (CN V), and lateral rectus muscle (CN VI) for electromyogram (EMG). Triggered, spontaneous, and neurotonic EMG responses are monitored and used for the identification of cranial nerves as well as to avoid injury. Tumor is dissected away carefully when in vicinity of these nerves without injuring them. Any bleeding can be controlled with warm saline irrigation and homeostatic agents (e.g., FlosealTM or SurgifloTM). In primary cases, the tumor is usually only attached to the endosteal layer surrounding the ICA. Stage 4 – Involvement of prestyloid parapharyngeal space above the lower border of the mandible and/or with minimal intracranial extension lateral to the superior orbital fissure a b In cases of such widespread tumor extension we employed multiple corridors or changed our strategy to an endoscopic‑assisted external approach. To this end, the surgical procedure can be divided into two steps, each tailored to the tumor extension. Clamping of external carotid artery on the same side is done to minimize the blood loss and should be done before starting the endoscopic procedure. For the transnasal corridor, again a modified Denker’s approach is used to expose the angiofibroma to its most lateral extent before tumor dissection is carried out. V2 is again identified and preserved. The tumor c is cleared from the sinonasal corridor step by step, as described above. Figure 2: Preoperative imaging in Janakiram staging system Stage 4a – Prestyloid parapharyngeal tumor extension above the (Stage 2c) tumor spread beyond the infratemporal fossa. (a) Tumor lower border of the mandible [Figure 5] spread along the greater wing of sphenoid. (b) Tumor spread in the 4a – In cases with parapharyngeal extension, a transoral corridor should inferior orbital fissure. (c) Tumor in the pterygoid fossa be adopted. In this approach, the tumor bulge is identified in the soft palate and an intraoral incision is made anterior to the anterior pillar. the JSS. A comparison of the JSS to other existing staging The mucosa, submucosa, and fibers of palatoglossus and superior systems is presented in Table 3. The subgrouping of the constrictor pharyngis are dissected to visualize and expose the tumor. With constant traction on the inferior part of the tumor, the mass is patients in stages is presented in Table 4. bluntly dissected along the tumor bed in the prestyloid space. It is then pushed superiorly to be delivered via the infratemporal fossa. The Imaging attachment of the tumor to any residual mass is now sharply cut near the On analysis of preoperative CT imaging studies of the foramen ovale. The intraoral part of the JNA – depending on its size – is entire cohort of 242 native JNA cases, the pterygoid wedge delivered intraorally or through the nasal cavity. Hemostasis is performed and floor of sphenoid sinus were the most commonly and the incision is closed in a water‑tight manner to prevent infection. involved skull base structures. On further detailed analysis Stage 4b – Minimal intracranial extension [Figure 5] of the imaging studies, it was noted that the epicenter of In cases with tumor extension through the superior orbital fissure the tumor could be localized to the pterygoid wedge in all into the intracranial compartment (middle cranial fossa and towards our cases. The vidian canal was identifiable as a separate the temporal lobe), the tumor can best be accessed via a transorbital endoscopic approach. An incision at the level of the brow or inferiorly structure in 19% of our JNA cases. to it is made to enter the supraorbital area. The periorbita is moved and The nasopharynx and the pterygopalatine fossa were elevated to allow drilling of the greater wing of the sphenoid bone. This involved in 98.4% and 95.8% of the cases, respectively. Contd... The tumor was observed to frequently extend via an Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 Table 3: Staging systems Classifications Stages Based on Approach No. of patients in retrospective analysis Sessions et al. I-III CT Open 12 Chandler et al. I-IV CT Open 13 Andrews et al. I-IV CT Open 14 Radkowski et al. I-III CT Open 23 Onerci et al. I-IV CT Endoscopic 36 Snyderman et al. I-V CT and pre/post‑embolization Endoscopic 35 angiogram Janakiram et al. I-IV CT With proposed endoscopic 242 stage‑wise surgical planning a b a b c c d e d f f Figure 4: Postoperative CT scans. (a) postoperative CT scan of a Stage 1a. (b) similar postoperative scans of stage 2b. (c) Stage 2c with extension in the IOF. (d) Postoperative CT scan stage 2c with extension to the pterygoid fossa. (e) Postoperative CT scan of stage e f 2c with extension to cheek. (f) Postoperative CT scan of a stage 3b JNA. (g) Postoperative CT scan of a stage 4a JNA Figure 3: Preoperative imaging in Janakiram staging system. (a, b) Axial and coronal views of tumor in the Meckel’s cave (Stage 3a). (c) Axial cut showing tumor engulfing the internal associated with involvement of the infratemporal fossa. carotid artery (Stage 3b). (d) Tumor seen extending in to the The pterygoid fossa was involved in 21.9% of the cases parapharyngeal space in a coronal section (Stage 4a). (e, f) Coronal and axial sections showing intracranial tumor extension in to the in our patient cohort. The greater wing of sphenoid was middle cranial fossa (Stage 4b) involved in 45.8% of the patients. Finally, we observed that the tumor extended from the pterygoid wedge along anterolateral pathway reaching into the infratemporal the greater wing of sphenoid into the middle cranial fossa fossa in 89.66% of the cases. Once tumor was present in in 2.1% of the patients. the infratemporal fossa, it showed multidirectional spread A second typical pattern observed was that of the tumor along pathways of low resistance. extending posteriorly towards the quadrangular space with erosion of the base of pterygoid and the greater Orbital extension through the inferior orbital fissure was wing of the sphenoid. The quadrangular space was found seen in 25.6% of the cases. This pathway was typically also to be involved in 30.1% of the cases. Tumors extending Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 Figure 5: Stage 1a – Coronal cut section showing JNA in the pterygoid wedge area and occupying the sphenoid sinus. Stage 1b – JNA in the pterygoid wedge area and extending to the nasopharynx. Stage 2a – JNA extending in the nasal cavity and minimal involvement of pterygopaltine fossa. Stage 2b – JNA extending to the pterygopalatine fossa. Stage 2c – JNA involving the infratemporal fossa. Stage 3a – JNA extending to the quadrangular space. Stage 3b – JNA engulfing the internal carotid artery. Stage 4a – JNA extending to the Prestyloid parapharyngeal space. Stage 4b – JNA extending intracranially Table 4: Patient distribution in various stages in our system Stage Extension No. Stage 1a Pterygoid wedge and/or paranasal sinus 3 Stage 1b With extension to nasopharynx 7 Stage 2a With extension in nasal cavity and/minimal involvement of pterygopaltine fossa 15 Stage 2b Involvement infratemporal fossa 21 Stage 2c Involvement infratemporal fossa with extension to check/pterygoid space/ 123 inferior orbital fissure/laterally along the greater wing of sphenoid Stage 3a Involvement of quadrangular space/Meckel’s cave 46 Stage 3b Involvement of cavernous sinus/Engulfing carotid artery 17 Stage 4a Prestyloid parapharyngeal tumor extension above the lower border of the mandible 5 Stage 4b Intracranial intradural extension 5 into the quadrangular space were located anterior to the Residual and recurrent tumor anterolateral wall of cavernous sinus. Involvement of the Out of the entire cohort of 242 cases, we observed cavernous sinus itself was quite rare and seen in only 19 cases with residual disease and 22 recurrent cases 6 cases. The most common segment of the ICA, which Table 6. During the early phase of our surgical experience showed some tumor involvement was the paraclival ICA. with endoscopic resections, we encountered residual and Please refer to Table 5 for a listing of the involvement of recurrent tumor most commonly located in the pterygoid various sites. wedge. A total of 10 such recurrences occurred in this Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 area. In the subsequent cases – which were performed Staged operation after we had gained substantially more endoscopic Seven patients underwent surgery that was planned as a experience – we drilled away the cancellous bone of the two‑step operation to begin with owing to the anticipated pterygoid wedge to ensure complete tumor removal, profound intraoperative blood loss during the primary which allowed us to significantly reduce the incidence surgery. There was a statistically significant correlation of residual and recurrent disease. As our surgical between the extent (stage) of the tumor on presurgical expertise evolved and more advanced tumors underwent imaging and the need for staging the procedure into endoscopic resections, tumor recurrences were noticed multiple operations. (fischer exact test P < 0.001) Please only in the superior orbital fissure, quadrangular space, see Table 8 for details. inferior orbital fissure, and surrounding ICA. Intraoperative blood loss The various sites of observed tumor recurrence are listed Intraoperative blood loss is an important outcome of surgery in Table 7. and helps to evaluate efficacy of a surgical approach. Residual tumor was found in only 19/242 cases on the Blood loss was measured carefully by accounting for both initial (36 hour) postoperative scan, and patients who the volume of blood that was aspirated during the surgery showed residual tumor burden, underwent a second surgery and for the amount of irrigation fluid that was used. Mean for excision. The group with residual disease constituted blood loss for each surgery according to the extent of 7.8% of the JNA cases of this series operated at our center. disease and JSS stage was calculated [Table 9]. A clear progressive increase in intraoperative blood loss Table 5: Involvement of the various sites in preoperative was observed with higher stages of disease/more advanced CT scan disease. The correlation of blood loss with extent of Site Number disease (stage) was studied for the newly proposed JSS Pterygoid wedge 241 as well as for other already existing staging systems; it Sphenoid sinus 240 became evident that blood loss correlated best with Nasopharynx 239 the stages in the JSS staging system when compared to Nasal cavity 232 others (r = 0.92 by Spearman rank correlation; Table 10). Intraoperative blood loss requiring blood transfusions Medial pterygopalatine Fossa 5 was seen from stage 2c, and the amount of blood loss Complete pterygoalatine fossa 227 increased with more extensive disease stages. Staged Infratemporal fossa 217 operations were planned and performed for tumors of Cheek 27 stages 4a and 4b in view of anticipated massive blood loss Temporal fossa 2 during the primary surgery and to give the patient some Pterygoid fossa 65 recuperation prior to complete tumor removal. Inferior orbital fissure 100 Orbit 61 DISCUSSION Vidian canal 217 Lateral recess 237 Owing to its dense vascularity and rather aggressive Greater wing of sphenoid 110 growth, JNA is a very challenging tumor – even for Quadrangular space 73 experienced surgeons. However, over the last years, a Meckel’s cave 11 striking paradigm shift in surgical management of JNA has Middle cranial fossa 28 occurred with new endoscopic and endoscopic‑assisted Superior orbital fissure 39 approaches performed by expert hands. With superior Cavernous sinus 28 surgical instrumentation available, better endoscopic Internal carotid artery 11 illumination techniques and substantially better direct Prestyloid parapharyngeal space above the lower border 5 vascular control methods, complete tumor removal can of mandible now be achieved for even very advanced cases of JNA, as Intracranial intradural extension 5 seen in our stages 3a and above. Table 6: Recurrence Stage 1 a Stage 1 b Stage 2 a Stage 2 b Stage 2 c Stage 3 a Stage 3b Stage 4a Stage 4b Total n 3 7 15 21 123 46 17 5 5 242 No recurrence 3 6 15 21 116 42 11 4 2 220 Recurrence 0 1 0 0 7 4 6 1 3 22 % of total recurrences 0.0 4.5 0.0 0.0 31.8 18.2 27.3 4.5 13.6 100 Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 The primary objective of a clinically meaningful extensive cohort of 242 JNA patients who were operated tumor staging system is to aid in determining the strictly endoscopically or with endoscopically‑assisted best management protocol as well as to prognosticate techniques at our center over the past 9 years. treatment outcome. After the introduction of the first A detailed preoperative CT scan analysis revealed the classification system by Sessions et al. in 1981, a number pterygoid wedge to be the most common site of residual of modifications were proposed. Among these, the tumor during the early phase of our surgical series. This modification proposed by Radkowski et al. in 1996 is the observation was made on follow‑up CT, and it was focally most widely accepted classification.[2,10,24] Approximately addressed endoscopically during the next cases as the a decade later, Onerci et al. developed another updated surgical technique evolved and as we became more radical classification in 2006, which was based on advances in our resection strategy. This knowledge was also applied made in imaging technology and the expanded use of to a small set of patients undergoing repeat surgeries. As endoscopes. Shortly thereafter, in 2008, Carrilo et al. we reinspected the pterygoid area, additional tumor could proposed yet another classification system in which tumor be identified at the pterygoid wedge, and more extensive size was identified as an independent prognostic factor. “in depth” drilling was performed for all these cases. Snyderman et al. then proposed a staging system based This led to no residual/recurrent tumor in this area on on their retrospective review of endoscopic and open subsequent CT imaging. In three cases, we observed that approaches. The authors concluded that two important JNA was limited to the pterygoid wedge and sphenoid factors (namely route of skull base extension and reduced on high‑resolution CT without any nasopharyngeal soft vascularity after embolization) can be used to predict the tissue involvement at all on endoscopy. This observation prognosis in angiofibroma patients. was confirmed repeatedly in our growing series and with Our staging system is predominantly pathoanatomical and longer follow‑up intervals, thereby revealing that the classifies tumors based on their topographic extension, as pterygoid wedge functions as the most likely site of origin seen on high‑resolution preoperative imaging. It divides of the tumor. JNA into distinct subgroups that represent progressively It is our impression that tumor growth occurs along more extensive tumor stages, and pairs each with a most certain tissue planes, which are those of least resistance. suitable surgical approach for definite care. This system Another mode of spread appears to be along the vascular is based on the surgical principle of to distinct subgroups channels in the nose and skull base. The pathway of that represent progressively more extensive tumor stages, progressive growth and extension of tumor mass with bone and pairs each with a most suitable surgical approach destruction in JNA is more a “pushing” pattern of growth for definite care. This system is based on the surgical rather than one of malignant infiltration and this explains principle of “centripetal dissection” and sequential that the tumor – when spreading intracranially – respects segmental resection. the barrier formed by the dura. We also analyzed the The tailored approach evolved in our institution over time pattern of tumor spread into anatomically complex areas and its applicability can be seen in the analysis of this such as the greater wing of the sphenoid, the quadrangular space, the cavernous sinus, and along the ICA. Table 7: Recurrence sites The tumor extension seen preoperatively on CT scan here Recurrence in stage n Area was correlated to what we saw endoscopically, and both Stage 1b 1 Pterygoid wedge modes of observation appeared congruent in their findings. Stage 2c 7 Pterygoid wedge, greater wing of sphenoid Therefore, it was concluded that a designated preoperative Stage 3a 4 Superior orbital fissure, quadrangular CT protocol of high quality and thin cut technique space, infratemporal fossa for both bone and soft tissue windowing can help the Stage 3b 6 Cavernous sinus, pterygoid fossa, superior surgeon to develop a clear strategy of how to approach orbital fissure this unique tumor in a stepwise manner. Once the tumor Stage 4a 1 Internal carotid artery pattern and extent can be fully appreciated, the surgical Stage 4b 3 Superior orbital fissure, pterygoid fossa, team merely has to follow the proposed technical steps middle cranial fossa, internal carotid artery and principles. Table 8: Staged operation Stage 1a Stage 1b Stage 2a Stage 2b Stage 2c Stage 3a Stage 3b Stage 4a Stage 4b Total N 3 7 15 21 123 46 17 5 5 242 Non-staged operation 3 7 15 21 123 46 17 3 0 235 Staged operations 0 0 0 0 0 0 4 2 5 7 % of total 0.0 0.0 0.0 0.0 0.0 0.0 0.0 30 70 100 Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 Table 9: Intraoperative blood loss according to stage and as the one employed by Radkowski. One reason may be blood transfusion that almost all endoscopic staging systems will assign any Stage Number Mean blood loss ml Blood transfusion area with intracranial high vascularity or with difficult access to a higher stage than other intracranial areas not Stage 1a 3 15.3 bearing these features. This differential staging does not Stage 1b 7 36.57 exist in older (nonendoscopic) staging systems, which Stage 2a 15 67.2 may explain their rather poor correlation to intraoperative Stage 2b 21 112.2 blood loss. Stage 2c 123 172.3 1-2 Stage 3a 46 293.1 1-4 It is generally accepted that the pterygoid wedge Stage 3b 17 1348.3 4-14 represents a watershed zone for blood supply of JNA Stage 4a and b 10 2919.1 4-16 feeder vessels. This observation is reflected in our strategy of a segmental resection, which follows the principle that tumor feeding vessels anterior to the pterygoid Table 10: Spearman R value for correlation between wedge can be well controlled in a single step by direct intraoperative blood loss and stage visualization and ligation. That is also the reason that we Staging system R value did not pursue embolization preoperatively. This strategy Janakiram et al. 0.92 will help avoid unwanted neurological sequelae that may Snyderman et al. 0.84 be caused by embolization. The tumor posterior can be Onerci et al. 0.80 further resected in a staged approach depending on the Rodkowski et al. 0.72 blood loss encountered. We observed that, here again, Andrews et al. 0.81 blood loss can be managed well by direct surgical ligation Chandler et al. 0.61 without increasing the procedural morbidity and without Sessions et al. 0.63 the need for embolization. Preoperative embolization has shown a reduction in This image‑based staging system emphasizes the intraoperative blood loss and a decrease in operative time in necessity of an accurate preoperative assessment of some studies, which will both facilitate complete excision. the lesion to truly understand the extent of tumor [7,11,13,14] However, a study by Lloyd et al. and another infiltration. It also allows to pay tribute to extensions by Borghei et al. suggested that the risk of recurrence into difficult to reach anatomical areas, which then increases in cases with preoperative embolization.[2,11,12] establishes the need to approach such extensive tumors This observation was later supported by Mann et al., and via multiple surgical corridors or the rare need for a some authors have since suggested that embolization can planned staged resection. lead to tumor being left behind at resection.[2,11] Blood loss is one of the most important outcome Another aspect that should be taken into account is that variables in JNA resections and a parameter which preoperative embolization is not without complications. depends not only on surgical skill but largely on Some major complications may occur such as common surgical strategies and stepwise surgical progress made iliac artery thrombosis, acute pulmonary edema, and intraoperatively.[2,29] preoperative anticipation of blood cranial nerve deficits. Other minor complications such loss is a prerequisite in diligent surgical planning and can as sore throat, hemifacial pain, temporomandibular joint determine the need for possible staging of any procedure. sourness, nasal alar necrosis, fever, and periorbital pain In our analysis, intraoperative blood loss correlated best have also been reported. At least three articles have with the stages, as proposed by the JSS, and was more also reported the debilitating complication of retinal accurate in predicting blood loss than previous staging artery occlusion and blindness following preoperative systems (r = 0.92) by Spearman rank correlation (from embolization for JNA.[21,25,30] The benefit of embolization results correlation between stage and blood loss). should, therefore, be carefully balanced against the risk of neurological complications in an otherwise histologically We found a consistent and positive correlation between benign tumor. the observed tumor stage and the amount of blood loss In a noteworthy study by Moulin et al., no significant encountered across each of the stages of our staging difference was noted with respect to intraoperative system. However, this finding is not in agreement with bleeding in JNA cases when embolized and nonembolized the observation by Snyderman et al. who found no groups were compared. consistent correlation between some staging systems and the respective blood loss. It was noted though that At our center, JNA cases were surgically treated endoscopic staging systems had a better correlation to without embolization, and intraoperative bleeding was intraoperative blood loss than older classifications, such addressed and managed by a multipronged strategy. The Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 administration of hypotensive anesthesia was found to changed to near to or in the quadrangular space, the help in decreasing intraoperative blood loss. External inferior and superior orbital fissure, the middle cranial carotid artery ligation can be performed in high‑staged fossa, and the cavernous sinus. To further decrease these tumors. Intraoperatively, control over tumor feeding rates, surgical approaches were modified by widening the vessels was achieved by diligent visualization with direct bony margins of, e.g., the inferior orbital fissure and with identification and ligation, and those in close proximity the diligent identification of a clean dissection plane of the ICA were cauterized using Kassam Bipolar that could be developed without the use of any cautery. forceps. Our surgical technique follows the principle of This clearly improved our ability to follow the tumor into a “centripetal dissection,” which enables the surgeon to complex and deep structures. Even in experienced hands, clearly identify the feeder vessels. Other maneuvers such we noted that, with more advanced and extensive tumor as optimal positioning of the patient, intraoperative warm stages, the residual and recurrence rates were unavoidable. saline irrigation, and the application of hemostatic agents The stagewise recurrence is given in Table 11. also contributed to the control of blood loss. JNA has a high propensity for recurrence with rates The assignment to a high stage in our system correlated reported as high as 32%. According to Ramezani well with the need of multiple‑staged operations and et al., this can be as high as 50% if JNA is invading the was found to be another robust variable. This aided infratemporal fossa, sphenoid sinus root of pterygoid, significantly in surgical planning and was also a relevant clivus, and cavernous sinus.[3,26] aspect of presurgical patient counseling. Operations for Owing to this high recurrence rate seen in some JNA, a extensive and high‑staged tumors were then broken down thorough and radical excision of the tumor with all its into multiple procedures in view of anticipated excessive extension should be attempted. Boghani et al. stated intraoperative blood loss in the primary surgery, and a in a comprehensive systematic review that, in purely second surgery was planned to achieve complete tumor endoscopic approaches, the recurrence rate ranges from excision. There was a statistically significant correlation only 0–23%. This number increases to 15–50% and between the stage of the tumor and the need to stage the 0–0% for endoscopic assisted and open approaches, operation as per the JSS (P < 0.001). respectively. Pryor et al. reported no recurrences in Surgical strategy is of paramount importance in managing 5 patients. Renkonen, however, had a 33.3% recurrence JNA and significantly affects the prognosis of this disease. rate. In a comparatively larger series of 46 patients Surgical confidence has increased with better anatomical operated endoscopically, Nicolai et al. observed a orientation skills and with increased experience in recurrence rate of 8.7%. Ardehali et al. reported, in endoscopic skull base tumor resections. Irrespective of their series of 47 patients, a recurrence rate of 19.1%. a particular surgical strategy or trajectory, the goal of all As an endoscope provides a magnified and multiangled surgical approaches is to achieve wide exposure and good viewing opportunity, tumor extensions can be much visibility for adequate vascular control and minimize better visualized than with a microscopic approach, and morbidity. Better visualization of JNA in cancellous we think that this aspect is a key feature in explaining bone, quadrangular space, cavernous sinus, and areas why the incidence of residual disease has been drastically where the tumor is engulfing the ICA has enabled reduced in well‑done endoscopic cases.[5,16] However, surgeons to adopt more aggressive approaches, even at present the statistical analysis is limited by only in complex areas, in hopes of complete excision with small number of patients which were reported in these minimal morbidity and mortality. Our study shows that studies. This is now corroborated by our series with a proactive and extensive (not to say aggressive) surgical a sizable patient cohort, in which a comparably low approach to JNA is feasible endoscopically, and that our recurrence rate of only 9.1% was achieved. approach results in excellent outcomes with minimal morbidity when performed by experienced hands. In this article we have made a sincere effort to propose a clinically meaningful JNA staging system, which The most important outcome, besides the patients’ correlates to clear operative guidelines that show that clinical status in the postoperative period, is the frequency most JNA can be managed endoscopically. Using these of observed tumor recurrences, which are often due to approaches and the currently available endoscopic inaccessible locations or under‑resected tumor margins due to high vascularity. By gaining more and more Table 11: Stagewise recurrence surgical experience with our cohort, we noticed a change Stage Recurrence/ No. of patients in the location of possible residual and recurrent disease. Initially, we noted that the pterygoid wedge was the most 1 1/10 common site. With increased understanding of the tumor 2 7/159 spread topography and more extensive posterior pterygoid 3 10/63 drilling, the sites for tumor recurrence (or small residuals) 4 4/10 Surgical Neurology International 2017, 8:55 http://www.surgicalneurologyint.com/content/8/1/55 technology, we have been able to reach as far as the Curr Opin Otolaryngol Head Neck Surg 2004;12:495‑9. 8. Hofmann T, Bernal‑Sprekelsen M, Koele W, Reittner P, Klein E, middle cranial fossa dura, parapharyngeal space, cheek, Stammberger H. Endoscopic resection of juvenile angiofibroma—Long term and temporal fossa. We believe that we have stretched results. Rhinology 2005;43:282‑9. the limits of minimal invasive resectability with such 9. Kasemsiri P, Prevedello DM, Ditzel L, Otto BA, Old M, Teknos T, et al. single or multicorridor endoscopic approaches. However, Surgical Treatment of Nasopharyngeal Malignancies: Role of Endoscopic Endonasal Approaches. J Nasopharyngeal Carcinoma 2014;1:e14. even in the most experienced hands, a few highly 10. Khoueir N, Nicolas N, Rohayem Z, Haddad A, Abou Hamad W. Exclusive extensive tumors cannot be accessed endoscopically endoscopic resection of juvenile nasopharyngeal angiofibroma: A systematic alone owing to their location and topography. For such review of the literature. Otolaryngol Head Neck Surg 2014;150:350‑8. tumors, we suggest to continue to employ external 11. Li JR, Qian J, Shan XZ, Wang L. Evaluation of the effectiveness of preoperative approaches, as recommended in the past.[5,4,8,16,22,23,27] embolization in surgery for nasopharyngeal angiofibroma. Eur Arch Otorhinolaryngol 1998;255:430‑2. Such tumors have hence been included as a separate 12. Lloyd G, Howard D, Phelps P, Cheesman A. Juvenile angiofibroma:The lessons standalone stage of our classification. of 20 years of modern imaging. J Laryngol Otol 1999;113:127‑34. 13. McCombe A, Lund VJ, Howard DJ. Recurrence in juvenile angiofibroma. CONCLUSION Rhinology 1990;28:97‑102. 14. Midilli R, Karci B, Akyildiz S. Juvenile nasopharyngeal angiofibroma: Analysis of 42 cases and important aspects of endoscopic approach. Int J Pediatr Surgical approaches in the endoscopic era have Otorhinolaryngol 2009;73:401‑8. revolutionized the management of JNA and have 15. Moulin G, Chagnaud C, Gras R, Gueguen E, Dessi P, Gaubert JY, et al. Juvenile improved surgical outcomes for extensive lesions. This nasopharyngeal angiofibroma: Comparison of blood loss during removal in embolized group versus nonembolized group. Cardiovasc Intervent Radiol study shows the importance of imaging in selecting the 1995;18:158‑61. most suitable surgical approach with results in reducing 16. Nicolai P, Berlucchi M, Tomenzoli D, Capiello J, Trimarchi M, Maroldi R, et al. morbidity and mortality in JNA surgery. Endoscopic surgery of Juvenile angiofibroma: When and how. Laryngoscope 2003;113:775‑82. To this end we propose in this paper the JSS that is 17. Nicolai P, Villaret AB, Farina D, Nadeau S, Yakirevitch A, Berlucchi M, et al. based on preoperative imaging characteristics obtained Endoscopic surgery for juvenile angiofibroma: A critical review of indications from data of one of the largest JNA case series to date. after 46 cases. Am J Rhinol Allergy 2010;24:e67–e72. 18. Nicolai P, Schreiber A, Bolzoni Villaret A. Juvenile nasopharyngeal angiofibroma: It reliably stratifies patients into treatment groups Evolution of management. Int J Pediatrics 2012;2012:412545. with definite surgical approaches, which redefine the 19. Ogawa AI, Fornazieri MA, da Silva LV, Pinna FR, Voegels RL, Sennes LU, achievable boundaries of endoscopic resection of JNA in et al. Juvenile angiofibroma: Major and minor complications of preoperative complex areas such as Meckel’s cave, cavernous sinus, embolization Rhinology 2012;50:199‑202. and ICA. It also aids in predicting outcomes. It is of 20. Onerci M, Oğretmenoğlu O, Yücel T. Juvenile nasopharyngeal angiofibroma: A revised staging system. Rhinology 2006;44:39‑45. further value as it reports unique observations regarding 21. Onerci M, Gumus K, Cil B, Eldem B. A rare complication of embolization presumed tumor origin and how this lesion spreads along in juvenile nasopharyngeal angiofibroma. Int J Pediatr Otorhinolaryngol preferred pathways. 2005;69:423‑8. 22. Onerci TM, Yucel OT, Ogretmenoglu O. Endoscopic surgery in the Financial support and sponsorship treatment of juvenile nasopharyngeal angiofibroma. Int J Pediatr Otolaryngol Nil. 2003;67:1219‑25. 23. Pryor SG, Moore EJ, Kasperbauer JL. Endoscopic versus traditional Conflicts of interest approaches for excision of juvenile nasopharyngeal angiofibroma. There are no conflicts of interest. Laryngoscope 2005;43:282‑9. 24. Radkowski D, McGill T, Healy GB, Ohlms L, Jones DT. Angiofibroma. Changes in staging and treatment. 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